As for production of proteins/enzymes, i.e., major components of various biological products, simple, easy and low-cost methods for their production have been sought, such as introduction of their genes, if they are isolated, into microorganisms, like E. coli, and letting the proteins/enzymes be expressed and accumulate in them. However, there are also many cases in which attempts fail to let a heterologous protein express/accumulate in the cells of microorganisms. The cause of such failures becomes particularly notable when higher production efficiency is sought. That is, the heterologous protein biosynthesized in the cells of a microorganism, which accumulates forming insoluble inclusion bodies, gets inactivated in the process. Generally, it is very difficult to solubilize such insoluble inclusion bodies of a protein and restoring the biological activity of the protein.
Further, in the case where the heterologous protein to be produced has a cytotoxicity, accumulation of that toxic protein adversely affects the proliferation/survival of the very host cells, resulting in lowered production yield, and further, in death of the host cells.
Due to these drawbacks, production of proteins/enzymes, which are major components of various biological products, often has to rely on time-consuming and costly methods, such as utilizing the living organisms that intrinsically produce the protein/enzyme. There seems to be not a small number of cases in which these drawbacks form a factor that hindering development of an efficient method of their industrial production, and this is one of the problems to be solved.
On the other hand, insecticidal proteins produced by an aerobic soil bacterium, Bacillus thuringiensis, has long been known (see as a review e.g., Non-patent Document 1). During its sporulation, Bacillus thuringiensis also produces, separately from spores, generally a single large parasporal inclusion body consisting mainly of a crystal protein (this is called “Cry protein”). Cry proteins consist of about 1000-1200 amino acids, and many of them are known to be produced by various Bacillus thuringiensis strains. About half of them have been found to have an insecticidal activity specific to certain insects, and some of those strains which produce a Cry protein having such an activity have been widely used as BT insecticides. When ingested by larvae of respective target insects, each of those Cry proteins which have an insecticidal activity undergoes cleavage by the digestive fluid at a predetermined position of its amino acid sequence and thus a peptide on its C-terminus side (consisting about 400-500 amino acids: abbreviated to “Cter”) is removed, leaving behind a peptide on the N-terminus side (NB: a short peptide at the N-terminus is also removed), which exhibits a potent insecticidal activity. For example, in the case of a protein named Cry4Aa, an N-terminus region consisting of Met 1 to Gln695 (in particular, a peptide left behind after Met1 to Try57 are removed) of its entire amino acid sequence acts as the very insecticidal component on its target insects (Culex pipiens pallens and the like). Its Cter, which consists of an amino acid sequence starting with Ile696 and is deleted by cleavage, is unnecessary part for the insecticidal activity (see Non-Patent Document 2). And, as for a protein known as Cry1Aa, which is an insecticidal specific to lepidopteran insects (butterflies and moths), the region consisting of Met1 to Lys621 on the N terminal side of its amino acid sequence (in particular, the part of the region left behind after further removal of Met1 to Arg28) works as the very insecticidal component, and its Cter, which consists of an amino acid sequence starting with Ala622, is deleted by cleavage (Non-Patent Document 3). Furthermore, as to Cry1Ac, which is also an insecticidal toxin specific to Lepidopteran insects (butterflies and moths) like Cry1Aa, its very insecticidal component consists of Met1 to Lys623 (in particular, the part of the region left behind after removal of Met1 to Arg28) of its amino acid sequence, and its Cter, which is located on the C-terminal side and consists of amino acid sequence starting with Ala624, does not take part in the generation of insecticidal activity, but is removed by cleavage by the action of the digestive fluid in the larvae (Non-Patent Document 4). Further, in recent years, Cry proteins have been found with which no insecticidal activity is as yet known, and some of them are found to specifically destroy human cancer cells, some specifically kill Tricomonas vaginalis, the pathogen protozoa causing human tricomonasis, and some exhibit a potent worm-killing activity to Nematoda. Though they differ in their biological activity and in their targets at which they exhibit toxic effects, the Cry proteins have a common characteristic property that they occur within Bacillus thuringiensis cells in the form of a large parasporal inclusion body.    [Non-Patent Document 1] M. Ohba, H. Hori and H. Sakai, “Bacillus thuringiensis: Science of Insecticidal Proteins”, Industrial Publishing & Consulting, Inc., Feb. 28, 2005.    [Non-Patent Document 2] M. Yamagiwa et al., Appl. Environ. Microbiol. 65: 3464-3469 (1999)    [Non-Patent Document 3] P. Grochulski et al., J. Mol. Biol. 254: 447-464 (1995)    [Non-Patent Document 4] J. N. Aronson and H. C. Arvidson, Appl. Environ. Microbiol. 53: 416-421 (1999)